Pharmacokinetics of Tasimelteon Alone and in Combination With a CYP3A4 Inhibitor, Ketoconazole, or a CYP3A4 Inducer, Rifampin.

NCT01637636 | Completed Phase 1

• 1 other identifier: VP-VEC-162-1112
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to understand whether there is any difference in the amount of tasimelteon (including its breakdown product) in the blood when taken alone and in combination with either rifampin or ketoconazole. Cytochrome P450 3A4 is an important enzyme produced by the body to breakdown certain medications. In this study, the effect that this important enzyme has on tasimelteon is being studied by assessing the effect rifampin and ketoconazole have on tasimelteon and how they are broken down by your body. Rifampin is a known inducer of Cytochrome P450 3A4 enzyme meaning that it increases the activity of the enzyme. Ketoconazole is a known inhibitor of Cytochrome P450 3A4 enzyme meaning that it decreases the activity of the enzyme. In addition, the safety and tolerability of tasimelteon will also be assessed throughout the study.

Conditions

Healthy

Keywords

rifampin,; ketoconazole,; CYP3A4,; tasimelteon,; VEC-162; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of tasimelteon and tasimelteon's metabolites with and without the CYP3A4 inhibitor ketoconazole.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose. Days 6 and 7: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours post-dose

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of tasimelteon and tasimelteon's metabolites with and without the CYP3A4 inducer rifampin.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose. Days 12 and 13: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours post-dose

Study Arms (2)

Rifampin

EXPERIMENTAL

Drug: tasimelteon; Drug: Rifampin

Ketoconazole

EXPERIMENTAL

Drug: tasimelteon; Drug: Ketoconazole

Interventions

tasimelteon DRUG

20mg, oral capsule, once, Days 1 and 12

Also known as: VEC-162, BMS-214778

Rifampin

Rifampin DRUG

600mg, oral capsules (2 x 300mg), once daily (QD), Days 2-11

Rifampin

Ketoconazole DRUG

400mg, oral tablets (2 x 200mg), once daily (QD), Days 2-6

Ketoconazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women ages 18 - 55 years, inclusive;
• Non-smokers;
• Subjects with Body Mass Index (BMI) of ≥18 and ≤35 kg/m\^2;
• Males, non-fecund females, or females of child-bearing potential using an acceptable method of birth control for a period of 35 days before the first dosing;
• Vital signs which are within the ranges shown below:
• Body temperature between 35.0-37.5 °C;
• Systolic blood pressure between 90-150 mmHg;
• Diastolic blood pressure between 50-95 mmHg;
• Pulse rate between 50-100 bpm.
• Ability and acceptance to provide written informed consent;
• Willing and able to comply with study requirements and restrictions;
• In good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis;

You may not qualify if:

• History of recent (within six months) drug or alcohol abuse;
• Any major surgery within three months of Baseline or any minor surgery within one month;
• History or current evidence of cardiovascular, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction or psychiatric disease judged by the Investigator to be clinically significant;
• History (including family history) or current evidence of congenital long QT syndrome or known acquired QT interval prolongation;
• Subjects who are currently considered a suicide risk, any subject who has ever made a suicide attempt, or those who are currently demonstrating active (within the past 6 months) suicidal ideation;
• Any condition requiring the regular use of medication except those listed in Section 8.2 of the protocol;
• Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of baseline
• Exposure (within 2 weeks of the Baseline Visit) to any over-the-counter medications including melatonin, dietary supplements and/or herbal remedies, except those listed on Section 8.2;
• Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening visit;
• History of intolerance and/or hypersensitivity to ketaconazole, drugs similar to ketoconazole (e.g. miconzaole or fluconazole), rifampin, tasimelteon, and/or drugs similar to tasimelteon including melatonin;
• Donation or loss of 400 mL or more of blood within one month prior to the Baseline Visit;
• Significant illness within the two weeks prior to Baseline;
• Pregnant or lactating females;
• History of porphyria or liver disease and/or positive for one or more of the following serological results:
• A positive hepatitis C antibody test (anti-HCV)

Sponsors & Collaborators

• Vanda Pharmaceuticals: lead

Study Sites (1)

QPS Bio-Kinetic Clinical Applications

Springfield, Missouri, 65802, United States

Location

MeSH Terms

Interventions

tasimelteon; Rifampin; Ketoconazole

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Piperazines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2012
• First Posted: July 11, 2012
• Study Start: June 1, 2012
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: February 17, 2014

Record last verified: 2014-02

Locations

US (1)